    3.6.1.12 | more |
construction of DCTPP1-deficient MCF-7 cells, which exhibit increased uracil misincorporation and an activation of the DNA damage response. Downregulation of DCTPP1 expression impairs proliferation and perturbs the dNTP pool of MCF-7 cells. Modulation of the dUTP/dTTP ratio reduces genomic instability. The downregulation of DCTPP1 has profound consequences on cell cycle progression, nucleotide pools. Phneotype of a bona fide DCTPP1-knockout (DCTPP1-KO) cell line derived from the HAP1 cell line, overview. HAP1 is a near haploid human cell line that is derived from the male chronic myelogenous leukemia (CML) cell line KBM-7, and deletion in exon 2 of the DCTPP1 gene is generated using the CRISPR/Cas9 technology. No differences in the pool of dGTP are observed between HAP1 wild-type and DCTPP1-KO cell lines. dUTP pool with potential genotoxic consequences is exclusively detected in deficient cells. The dCTP pool is similar for HAP1 wild-type and DCTPP1-KO cell lines. DCTPP1-knockout cells exhibit normal proliferation in spite of an imbalanced nucleotide pool. DCTPP1-KO cells exhibit a hypermutator phenotype. The activation of the DNA damage response upon DCTPP1 inactivation can be reverted by the expansion of the dTTP pool or defects in uracil excision. Phenotypes, detailed overview |
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